Expert Review of Gastroenterology & Hepatology最新文献

Introduction: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by the immune-mediated destruction of small and medium intrahepatic bile ducts, involving predominantly females. PBC has long been described as an autoimmune liver disease, also because it is very often associated with many autoimmune conditions. More recently, another pathogenic mechanism exploring the damage of cholangiocytes has been hypothesized, i.e. a defect in the biliary umbrella which is physiologically responsible for the exchange of the ions Cl^- and HCO₃^- and maintains the integrity of glycocalyx. To provide a state-of-the-art analysis of this topic, a systematic review of literature in PubMed, Scopus, and Science Direct was conducted (inclusive dates: 1986-2023).

Area covered: Although the etiology remains unknown, pathogenesis consists of a complex immune-mediated process resulting from a genetic susceptibility. PBC can be triggered by an immune-mediated response to an autoantigen, which leads to a progressive destruction of bile ducts and eventually to a progressive fibrosis with cirrhosis. The defect in the 'bicarbonate umbrella' acts as a protection against the toxic hydrophobic bile acids, leading to a toxic composition of bile.

Expert opinion: This review offers a summary of the current knowledge about the pathogenesis of PBC, indicating that this is probably based on the mutual relationship between the immune insult and the unbalanced secretory mechanisms.

Introduction: Inflammatory bowel disease (IBD) is a chronic disease characterized by the presence of systemic inflammation, manifesting not only as gastrointestinal symptoms but also as extraintestinal bone complications, including osteopenia and osteoporosis. However, the association between IBD and osteoporosis is complex, and the presence of multifactorial participants in the development of osteoporosis is increasingly recognized. Unlike in adults, delayed puberty and growth hormone/insulin-like growth factor-1 axis abnormalities are essential risk factors for osteoporosis in pediatric patients with IBD.

Areas covered: This article reviews the potential pathophysiological mechanisms contributing to osteoporosis in adult and pediatric patients with IBD and provides evidence for effective prevention and treatment, focusing on pediatric patients with IBD. A search was performed from PubMed and Web of Science inception to February 2023 to identify articles on IBD, osteoporosis, pediatric, and fracture risk.

Expert opinion: A comprehensive treatment pattern based on individualized principles can be used to manage pediatric IBD-related osteoporosis.

Introduction: Duodenal biopsy is the gold standard in the diagnosis of celiac disease, with increasing utilization of serology. A gluten challenge may be required, for example, when dietary gluten reduction precedes appropriate diagnostic evaluations. Evidence on the best challenge protocol is currently sparse. Pharmaceutical trials in recent years may have provided new insights into the challenge and advanced the development of novel sensitive histological and immunological methods.

Areas covered: This review outlines the current perspectives on the use of gluten challenge in the diagnosis of celiac disease and explores future directions in this area.

Expert opinion: Comprehensive elimination of celiac disease before dietary gluten restriction is essential to avoid diagnostic uncertainties. Gluten challenge continues to have an important role in certain clinical scenarios, although it is important to understand its limitations in the diagnostic evaluation. The evidence so far permits no unequivocal recommendation considering the timing, duration, and amount of gluten used in the challenge. Thus, these decisions should be made on a case-by-case basis. Further studies with more standardized protocols and outcome measures are called for. In the future novel immunological methods may help to shorten or even avoid gluten challenge.

Introduction: Liver disease is known as one of the leading co-morbidities in HIV infection, with 18% of non-AIDS-related mortality. There is constant crosstalk between liver parenchymal (hepatocytes) and non-parenchymal cells (macrophages, hepatic stellate cells, endothelial cells), and extracellular vesicles (EVs) are one of the most important ways of cell-to-cell communication.

Areas covered: We briefly cover the role of EVs in liver disease as well as what is known about the role of small EVs, exosomes, in HIV-induced liver disease potentiated by alcohol as one of the second hits. We also touch large EVs, apoptotic bodies (ABs), in HIV-induced liver injury, the mechanisms of their formation and potentiation by second hits, and their role in the progression of liver disease.

Expert opinion/commentary: Liver cells are an important source of EVs, which may provide the connection between different organs via secretion into the circulating blood (exosomes) or serve for the communication between the cells within the organ (ABs). Understanding the role of liver EVs in HIV infection and the involvement of second hits in EV generation would provide a new angle for the analysis of HIV-related liver disease pathogenesis and progression to end-stage liver disease.

Introduction: Hepatocellular carcinoma (HCC) is the most common liver-related cancer and the third leading cause of worldwide cancer-related mortality.

Areas covered: There have been many updated guidelines on the management of HCC in the past few years. Given the increasing burden of HCC in clinical practice, knowledge of evidence-based standards of care for these patients is essential for any practitioner managing patients with HCC. Early detection and judicious treatment based on the stage of the HCC can improve patient outcomes. We performed a PubMed (MEDLINE database) search for the latest guidelines related to the screening, detection, diagnosis, staging, and management of HCC. We aim to highlight some major considerations and common mistakes in managing HCC and attempt to provide evidence-based recommendations.

Expert opinion: The field of HCC management is expected to evolve in the coming years. Increased emphasis on personalized treatment and precision medicine with earlier detection methods, the development of noninvasive diagnostic tools, increased focus on combination therapies and a shift toward more targeted treatments will become more critical.

Introduction: Chronic hepatitis B (CHB) is rarely cured using available treatments. Barriers to cure are: 1) persistence of reservoirs of hepatitis B virus (HBV) replication and antigen production (HBV DNA); 2) high burden of viral antigens that promote T cell exhaustion with T cell dysfunction; 3) CHB-induced impairment of immune responses.

Areas covered: We discuss options for new therapies that could address one or more of the barriers to functional cure, with particular emphasis on the potential role of immunotherapy.

Expert opinion/commentary: Ideally, a sterilizing cure for CHB would translate into finite therapies that result in loss of HBV surface antigen and eradication of HBV DNA. Restoration of a functional adaptive immune response, a key facet of successful CHB treatment, remains elusive. Numerous strategies targeting the high viral DNA and antigen burden and aiming to restore the host immune responses will enter clinical development in coming years. Most patients are likely to require combinations of several drugs, personalized according to virologic and disease characteristics, patient preference, accessibility, and affordability. The management of CHB is a global health priority. Expedited drug development requires collaborations between regulatory agencies, scientists, clinicians, and within the industry to facilitate testing of the best drug combinations.

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) is a commonly performed procedure for pancreaticobiliary disease. While ERCP is highly effective, it is also associated with the highest adverse event (AE) rates of all commonly performed endoscopic procedures. Thus, it is critical that endoscopists and caregivers of patients undergoing ERCP have clear understandings of ERCP-related AEs.

Areas covered: This narrative review provides a comprehensive overview of the available evidence on ERCP-related AEs. For the purposes of this review, we subdivide the presentation of each ERCP-related AE according to the following clinically relevant domains: definitions and incidence, proposed mechanisms, risk factors, prevention, and recognition and management. The evidence informing this review was derived in part from a search of the electronic databases PubMed, Embase, and Cochrane, performed on 1 May 20231 May 2023.

Expert opinion: Knowledge of ERCP-related AEs is critical not only given potential improvements in peri-procedural quality and related care that can ensue but also given the importance of reviewing these considerations with patients during informed consent. The ERCP community and researchers should aim to apply standardized definitions of AEs. Evidence-based knowledge of ERCP risk factors should inform patient care decisions during training and beyond.

Introduction: Colonoscopy can cause psychological distress in patients, consequently discouraging patients from undergoing an unpleasant procedure or reducing compliance with follow-up examinations. This rapid review aimed to assess the feasibility and efficacy of Virtual Reality (VR) interventions during colonoscopy on patients' perceived psychological distress and procedure satisfaction.

Areas covered: We searched PubMed, CINAHL, ProQuest/All Databases, and Cochrane Library databases on 1 December 2022, with a date limiter of 2002-2022 for articles that investigated the effect and feasibility of any type of immersive VR-based intervention on patients' pain, anxiety, discomfort, and procedure satisfaction immediately before, during, and/or post-procedure of colonoscopy.

Expert opinion: Initially, 118 articles were identified, of which seven were eligible and included in this rapid review. Our findings demonstrate that VR interventions during colonoscopy were feasible, significantly reduced participant pain and anxiety, and significantly increased participant satisfaction with the procedure. VR interventions appear to be an effective alternative for patients who prefer to avoid analgetic medications or as an adjunct to routine sedation during colonoscopy. Directions of research design should focus on an optimized blinding process, using the high-end technology of 3-dimensional devices, considering an audiovisual distracting intervention, and designing multicenter and high-quality Randomized Controlled Trials.

Introduction: Irritable bowel syndrome (IBS) is characterized by chronic symptoms (>6 months) of abdominal pain in combination with a disturbed bowel habit. There is an association between the intensity of abdominal pain and the need for health care utilization. A bidirectionally disordered gut-brain interaction is central in the pathophysiology of IBS where a number of factors, gastrointestinal and non-gastrointestinal, can contribute to the illness experience. In order to treat abdominal pain in IBS, mapping these factors in a multidimensional clinical profile is helpful.

Areas covered: This review covers basic epidemiology and pathophysiology of abdominal pain in IBS, the diagnostic approach, and a multidimensional treatment model where the management of abdominal pain is in focus.

Expert opinion: A personalized treatment of abdominal pain in IBS is possible in patients who understand the diagnosis, the potential of therapies used, and where a good continuity in the patient-doctor relationship is established.

Introduction: As the pediatric obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in childhood. Pediatric NAFLD pathophysiology is tangled and still unclear, but insulin resistance (IR), genetics, epigenetics, oxidative stress, and inflammation act as key players. Due to the increased cardiometabolic risk of these patients, several biomarkers have been proposed for early NAFLD identification, but their clinical utility is poor. Recently, hepatic dysregulation of microRNAs (miRNAs) has been linked to metabolic dysfunction, which in turn implied in NAFLD development. Evidence on the intriguing role of miRNAs in NAFLD pathogenesis has emerging especially in at-risk children such as those with obesity. However, pediatric evidence supporting their potential use as early noninvasive NAFLD tools is still limited but promising.

Areas covered: We provided an overview on the emerging role of miRNAs in pediatric NAFLD by addressing some issues regarding their pathophysiological link with the metabolic milieu and their role as reliable NAFLD markers in children with obesity.

Expert opinion: Strong evidence supports a potential role of miRNAs as early biomarkers of NAFLD in children with obesity. They might represent a valid diagnostic and targeted therapeutic tool due to its close pathogenic link with the metabolic milieu.